Scientists have made several advances in designing a class of HIV vaccines that could offer broad protection against the virus, four new studies published recently in the journals Science, Science Translational Medicine and Science Immunology show. The methods used focus on generating broad-spectrum neutralizing antibodies, and one of these proposals is already in the clinical trial phase.
The strategy consists of inducing an immune system response that generates highly effective defenses to combat the virus, without the need to maintain continuous therapy. Current treatments manage to keep HIV undetectable, but must be administered for life.
The HIV epidemic is now in its fifth decade and during this time scientists have dedicated many resources to the development of vaccine candidates to combat the virus. However, health authorities still do not have an approved and effective formula that induces broadly neutralizing antibodies capable of neutralizing the most common strains of HIV.
“All attempts that have been made to obtain preventive vaccines against HIV have failed for decades. These studies provide data on new and different strategies to obtain broadly neutralizing antibodies against HIV. Everything seems to indicate that they could be an option that could be effective in preventing HIV infection,” José Alcamí, virologist and director of the AIDS Immunopathology Unit of the Carlos III Health Institute, and principal investigator, told SMC Spain. of the CombivacS heterologous regimens study, which has not participated in any of the investigations.
In the opinion of Mariano Esteban, virologist at the National Center for Biotechnology (CNB-CSIC): “The limitations are imposed by preclinical trials in animal models that, although necessary and important, do not exactly reflect what happens in humans. However, the data provided favors the use of these protocols in clinical trials, already underway,” he stated in statements to the same medium. And he adds that “the clinical results will tell us how far we have come with this type of vaccine approach of progressive immunizations. “A light of hope opens towards the understanding of how to better attack HIV after so many years since its identification as the causal agent of AIDS in 1983.”
What does the new HIV vaccine strategy consist of?
In the first paper published in Science, Jon Steichen and colleagues evaluated the protective effects of a new germline-targeting strategy based on the N332-GT5 trimer, a component of the HIV viral envelope. Taking a different approach in the second Science study, Zhenfei Xie and her colleagues showed that they could prime B cells with N332-GT5 via mRNA, delivered via lipid nanoparticles.
The solution involves a process called germline targeting, where scientists use immune-directed proteins (immunogens) to guide and prime young B cells as they mature in sites called germinal centers, with the goal of inducing to produce broadly neutralizing antibodies against HIV.
“These studies provide data on new and different strategies to obtain broadly neutralizing antibodies against HIV. Everything seems to indicate that they could be an option that could be effective in preventing HIV infection.”
Julià Blanco, Head of the Virology and Cellular Immunology group at the IrsiCaixa AIDS Research Institute, who has not participated in any of the studies either.
explains in statements to SMC Spain that “this strategy is already known and has been used previously. The HIV envelope protein has different regions that are recognized by neutralizing antibodies. For a specific region (the CD4 binding site), this strategy had already been used and has even reached human studies.”
Blanco adds that “we now have a second region (the base of the V3 loop) that can also be used in a similar way. “If both strategies are combined, a greater quantity and diversity of these neutralizing antibodies could be generated, which would make a potential vaccine more effective.”
In research published in Science Translational Medicine Christopher Cottrell and his colleagues designed a new nanoparticle immunogen as a booster for germline-targeted HIV vaccines. Finally, in work published in Science Immunology, Xuesong Wang and her colleagues showed that they could administer eOD-Gt8 60mer as an initial priming immunogen using mRNA encapsulated in lipid nanoparticles.
